Retinol (vitamin A) is an endogenous compound which occurs naturally in the human body and is essential for normal epithelial cell differentiation. Natural and synthetic vitamin A derivatives have been used extensively in the treatment of a variety of skin disorders and as skin repair and renewal agents. Retinoic acid has been used to treat a variety of skin conditions such as acne, wrinkles, psoriasis, age spots and skin discoloration.
Within the cells, retinol and retinoic acid are bound to specific cellular binding proteins, 2 of the major proteins are CRABP-1 and 2 (Roos et al., Pharmacological reviews: 50, 315-333, 1998). These proteins act in regulating the intracellular concentration of retinoids by acting as both storage or shuttle proteins in retinoid metabolism. The levels of this protein are regulated by the amount of retinoic acid within the cells. Higher cellular levels of retinoids increase the expression of CRABP-2. Therefore, the amount of this protein in the cells, is a measure of the retinoid activity of the cells. Skin cells contain CRABP-2 both in the epidermis and the dermis. CRABP-2 response to retinoid administration in fibroblasts in vitro is used as a reproducible measure of retinoid bioactivity that predict human skin responses (Elder et al., J. Invest. Dermatol., 106: 517-521, 1996). Therefore, CRABP-2 expression of fibroblasts is a measure of retinoid activity leading to various cosmetic skin benefits (antiaging, anti wrinkling, skin conditioning etc.).
Cosmetic compositions containing mulberry and retinoids have been disclosed. See for instance EP 815838 (Shiseido), EP887070 (Kibun Food Chemifa Co.), U.S. Pat. Nos. 5,676,948, 5,676,949, and 5,607,692. U.S. Pat. No. 5,332,575 discloses a method of targeting melanocytes with a compound containing a fucose residue to bind the product to the melanocyte membrane. A cosmetic composition is exemplified containing dry mulberry root bark extract at 0.5% level. In another example, beta carotene or 0.25% vitamin A propionate is employed.
The present invention is based in part on the discovery that mulberry extract in combination with selected retinoids exhibit synergy, when combined within a specific ratio range.